“The GCRF START grant has initiated a beautiful story and this story involves developing African scientists, especially in terms of Synchrotron Radiation Technology and Research. We hope to continue this highly fruitful collaboration for many years to come.”Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand
I love teaching and research, especially contributing towards human development through innovative research in medicine and biology. My research focuses on the Biochemistry and Structural Biology of druggable proteins of human Neglected Tropical Diseases (NTD’s) and ESKAPE pathogens (Healthcare Acquired Infections) at the University of the Witwatersrand’s Protein Structure-Function Research Unit (PSFRU). I owe my motivation for biochemistry to very good teachers and mentors from an early point in my education.
I was educated to undergraduate level in biochemistry at Nigeria’s Abia State University, Uturu, Abia State and as an undergraduate, found pleasure in being taught by biochemistry lecturers who were able to ‘self-de-elevate’ and inspire us. These teachers were easy to have rapport with and I was able to extract as much as they could offer, both as my teachers, as well as my mentors and motivators. I remember Dr Okechukwu Ukairo, a young and admirable biochemistry lecturer who taught us carbohydrate metabolism and bioenergetics. His persona as a biochemistry lecturer and researcher enabled him to de-mystify what was a difficult course in biochemistry by being down to earth, but not to be trampled upon!
Subsequently, I spent four years in Lesotho as an educator, teaching in secondary schools after briefly working as an analytical chemist at Lesotho Pharmaceuticals in Mafeteng. My desire to do my Master’s in Biochemistry was fulfilled, however, at the University of KwaZulu-Natal in Durban, South Africa, where I gained my PhD in 2008. Working with Prof Heini Dirr at Wits University (March 2009) strengthened my aspiration in Structural Biology and three years later, I joined The University of the Witwatersrand. Currently, I am a Senior Researcher and the Interim South African Research Chair (SARChI) in Protein Biochemistry and Structural Biology.
When I look back at my career journey so far, it was the experience of having inspiring teachers and mentors that stayed with me to the present day and drives my vision as head of my group in teaching, supervising and mentoring the students on my watch. Therefore, the GCRF START grant with its emphasis on equipping and mentoring the next generation of scientists in Africa to tackle local and global challenges, means everything to me, especially in terms of structural biology.
African scientists have a critical role to play in the search to solve Africa’s challenges
“My vision is to see young people rise-up and flourish in the sciences on the African continent and apply the African, UK and global perspectives we share in the GCRF START network to the global challenges we face.” – Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand
With the START grant I believe we can create a new narrative of excellence in African science and structural biology and fulfil our vision to equip our students in the latest techniques to solve our continent’s health, energy and socio-economic challenges. For example, at the PSRU, we have many gifted post-docs and undergraduates with the potential to go far and make a positive difference on our continent and beyond. I supervise 12 students (four PhD and seven MSc. students, and one Post-Doctoral Fellow), some of whom already benefit from the exposure to state-of-the-art synchrotron techniques at the UK’s national synchrotron – Diamond Light Source (Diamond) – as a result of the GCRF START grant. Often from previously disadvantaged backgrounds and female, these students have attended START funded workshops, have collected data remotely, and are being trained by scientists from the Diamond beamlines. They would love to one day visit Diamond to see a synchrotron for themselves and want to develop careers in structural biology and biochemistry.
Our dream is that each university in South Africa and beyond our borders will have new generation structural biology, synchrotron and drug discovery techniques taking place as a matter of course. In South Africa, our vision is to include lesser known universities like Venda, Fort Hare, and Johannesburg ensuring that those previously unable to access to opportunities will be able to do so. Already, in just over two years, the START network has grown in South Africa to encompass a wide range of university groups/hubs covering a broad variety of research disciplines to address challenges across Africa, as well as globally.
Take viruses like COVID-19, for example, we have every potential to be able to produce the targeted, appropriate vaccines and drugs needed for our unique situations. Instead of researchers from Europe and America coming to us to collect samples to take over to Europe/America to do their studies, we could be on an equal footing and able to do every stage of the research right here in Africa so that we are well prepared for outbreaks when they occur.
In terms of our journey at the PSFRU, the GCRF START grant and Diamond Light Source came at the right time for our group, and for me personally. When I got involved with START in 2018, most of my protein crystal structures were solved in-house using a home-source XRD Wits University commissioned in 2008. However, over the years, the life of the machine started depreciating and we had to look for an alternative light source. Prof. Yasien Sayed, Director of the PSFRU, was contacted by START Co-I, Prof. Trevor Sewell, from the University of Cape Town to champion the University of the Witwatersrand’s Structural Biology collaboration with Diamond as part of the South African broader collaboration with the facility, and because Prof. Sayed and I work in the same research unit, he involved my research in his application.
The common denominator is science!
“I know some people say that the priorities in Africa are all about hunger, and that doing scientific research is not a priority but if you look at all the challenges here, the common denominator is science!” – Dr Ikechukwu Anthony Achilonu, Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand
We can’t do without the science and the latest scientific equipment in terms of tackling Africa’s sustainable development goals. Take hunger and the goal of food security, for example. We need drought resistant crops and pest resistance; we need clean water sources and uncontaminated land; we need disease solutions for the animals and a healthy variety of nutritional and affordable crops; we need people who are sufficiently healthy to grow the food, distribute, manufacture and sell it. Indeed, some of the pathogens I am working on right now, such as Schistosomiasis (Bilharzia), affect a prime source of food security on our continent – cattle. The poultry industry is another example where multiple pathogens kill the poultry which people rely on for food. Therefore, investing in science in Africa is imperative for the health of our continent and the world.
However, sustainable sources of funding are needed to conduct world class science. Even in terms of small things like shipping samples, it costs over 3500 Rand (£160.00) each time we ship our protein crystals to and from Diamond. This would be prohibitive for many science groups if it were not for grants like GCRF START. The fact that START grant enables us to do the experiments remotely at Diamond, means we can save money – we don’t have to fly abroad to conduct our experiments and we speak the same language so there are no ‘lost in translation’ issues!
To demonstrate some of the diverse and world class science research we do at the PSFRU I have outlined three examples below, which benefit from the GCRF START grant.
Exploring language and cognition: untangling the neuromolecular networks in the brain
Dr Sylvia Fanucchi’s research looks in detail at a particular node of interaction that is implicated in Autism. This involves investigating the FOXP family of transcription factors which are associated with language and cognition. Her studies aim at untangling the neuromolecular networks in the brain by identifying the nodes of interactions associated with these proteins. In order to do this, Dr Fanucchi explores protein-protein interactions and protein-nucleic acid interactions and how they influence each other in these large neuromolecular complexes. Through the GCRF START grant using the Diamond synchrotron, Dr Fanucchi can investigate the structures of both protein-DNA and protein-protein complexes. This information is highly valuable in dissecting the interactions within these neuromolecular complexes at atomic resolution and is critical to answering the questions posed by Dr Fanucchi in her research.
New insights into the South African HIV-1 subtype C protease
Another example of success is Prof. Yasien Sayed’s research on the HIV C protease1 – the strain of the HIV virus we have in South Africa, whereby Prof Sayed and his team are the first to solve the type C protease at unparalleled resolution. This is a significant success (pending publication) which has been made possible with access synchrotron techniques at Diamond with the GCRF START grant2. This paves the way to repurpose AntiRetrovirals (ARV’s) that are tailor-made for the type of HIV we have here in South Africa so that in years to come, HIV prevention and treatment can be far more effective than they are now. Currently, the ARV’s employed here in South Africa are not tailored specifically for our strain of the HIV virus, which means that the side effects are more than they should be (leading to problems with ARV adherence) and drug resistance.
Schistosomiasis/Bilharzia – solving the 3D structure of the Schistosoma japonicum Glutathione S-transferase (GST ) protein
“Access to facilities at Diamond has enabled young and emerging researchers, such as Dr. Achilonu in my Unit to realise their potential by publishing their research in internationally peer-reviewed journals.” –Prof. Yasien Sayed, Director of the Protein Structure-Function Research Unit (PSFRU), University of the Witwatersrand, South Africa
There are several milestones yet to be reached but my journey with the GCRF START grant is already yielding fruitful outcomes for Africa. My publication3 titled “Molecular basis of inhibition of Schistosoma japonicum glutathione transferase by ellagic acid: insights into biophysical and structural studies” is one of those milestones achieved over the past three years. Using I03 & I04 beamlines at Diamond, we were recently able to solve the 3D structure of the Schistosoma japonicum GST protein at an unprecedented resolution of 1.53 Å- amongst the highest resolution in the current global protein database for this enzyme!
The resulting publication emphasises the need to exploit the unique structural diversity between Schistosoma GST and other human GSTs for a rational approach to design new generation anthelminthics. Without the high-resolution structure of the Schistosoma GST-in-complex with the potential natural product (Ellagic Acid) – which we aim to study for the design of new anti-Schistosoma drugs – it would have been difficult understanding several empirical observations made in our research. Achieving these results means we can now progress further to find effective drug targets, something only possible to the level we need using synchrotron techniques. I am very grateful to the GCRF START grant and Diamond for this opportunity.
Our vision to collaborate with groups in other African countries is also progressing. One such group is a medical research institute working on Schistosoma in Kenya with whom we hope to have a collaboration up and running by early next year. Now that we have new insights afforded by the solved structure of the Schistosoma japonicum GST protein, we need to know that the drug target we are investigating is active against an entire parasite – either as a parasite on its own or in an animal. A collaboration with the Kenyan group offers exciting opportunities to explore this. I also have students from Nigeria, Zimbabwe and Namibia who will be joining us next year; and one from India, therefore our group is truly pushing the boundaries geographically as well as scientifically!
Towards an African Light Source
For many, the ultimate vision is having an African Synchrotron Light Source on the African continent. However, it may take years before this is possible and therefore, in the meantime, the START grant enables us to move closer to fulfilling our vision to inspire creative and collaborative scientific research and equip the next generation of scientists in structural biology (and energy materials) to use synchrotron equipment and techniques. I pray and hope that GCRF START and Diamond continue this incredible journey with us, long into the future.
Read more here about the UN’s Sustainable Development Goals.
More about Dr Achilonu
Dr Ikechukwu Anthony Achilonu is Senior Researcher and the Interim South African Research Chair (NRF/SARChI) in Protein Biochemistry and Structural Biology at the Protein Structure-Function Research Unit (PSFRU), School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand in South Africa.